Protective effect of latex proteins from Plumeria pudica against acetaminophen-induced acute liver injury.

Abstract

The protein fraction from Plumeria pudica latex (LPPp) was evaluated against APAP-induced liver injury in mice. Key measurements included total leukocyte count, liver weight, AST, ALT, liver levels of MDA, GSH, SOD, MPO, NO3/NO2 concentration, cytokines TNF-α, IL-β, IL-6, IL-10, IFN- γ, and CXCL1. Histopathological and immunohistochemical analysis were conducted, and proteins in LPPp were identified by mass spectrometry. Molecular docking analyses were performed with LPPp proteins and APAP, NAPQI, TNF-α, and IFN-α. LPPp reduced liver weight, ALT, and AST levels, and prevented the decrease in total leukocyte count, indicating protection against liver injury. It also reduced MDA levels and preserved GSH and SOD levels, showing its antioxidant properties. LPPp significantly inhibited MPO and NO3/NO2 levels, reducing inflammation. LPPp decreased levels of TNF-α, IL-β, IL-6, IFN-γ, and CXCL1, while IL-10 levels remained elevated, suggesting an anti-inflammatory response. Histological analysis showed preserved liver tissue, and anti-Ly6C immunostaining indicated reduced neutrophil accumulation. Molecular docking revealed that latex cysteine proteases had a higher affinity for APAP and NAPQI, while a proteinase inhibitor showed affinity for CYP2EI, TNF-α, and IFN-α. These findings suggest that LPPp protects against APAP hepatotoxicity by interfering with APAP and NAPQI metabolism, reducing oxidative stress and inflammation, thus preventing hepatocyte damage.